2-Chlorobenzyl chloride → 7-Chloro-2-ethyl-1H-indene

HRID 991987Notes

Reaction equation

HRID 991987 reaction equation
C([O-])(=O)CCC.[Na+].C([N-]C(C)C)(C)C.[Li+].[CH3:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].C1COCC1.C(C1C=CC=CC=1)C.[Cl:36][C:37]1[CH:44]=CC=C[C:38]=1[CH2:39]Cl.O=S(Cl)Cl>C1COCC1>[CH2:17]([C:18]1[CH2:39][C:38]2[C:20]([CH:19]=1)=[CH:21][CH:22]=[CH:44][C:37]=2[Cl:36])[CH3:16]

Participants

7

Reactant 5

HCID 119062-Chlorobenzyl chlorideHCID 24386Thionyl ChlorideHCID 2724682Lithium diisopropylamideHCID 5222465Sodium ButyrateHCID 22742125Tetrahydrofuran heptane ethylbenzol

Product 1

HCID 121494117-Chloro-2-ethyl-1H-indene

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 12 L round-bottom flask was equipped with a mechanical stirrer, thermometer and reflux condenser. 385 g sodium butanoate (3.5 mol) and 2 L THF were added to form a slurry. 2.625 L lithium diisopropylamide, 2M in heptane/ THF/ethyl-benzene (5.25 mol, 50% excess) were added at ambient temperature, and then stirred for 24 hours. Then 705 g 2-chlorobenzyl chloride (4.375 mol, 25% excess) was added, and the reaction stirred for another 24 hours. Once completed, the reaction was quenched by adding 1500 mL H2O, and the solution allowed to separate. The aqueous layer, pH=13, was separated and neutralized by addition of 12N HCl to obtain pH=7.0, at which point a phase separation occurs. 2-(2-chlorobenzyl) butanoic acid was concentrated in the organic layer. Synthesis of 2-ethyl-7-chloroindene was completed by the same sequence of reactions and method as described in Example 1, beginning with the addition of SOCl2. See FIGS. 1 and 3. The product, 2-ethyl-7-chloroindene, was obtained by distillation at 110-114° C. under 1-3 mm Hg. Yield was 205 g (33% overall) of a clear, colorless oil.

Workup

  1. customA 12 L round-bottom flask was equipped with a mechanical stirrer
  2. temperaturethermometer and reflux condenser
  3. customto form a slurry
  4. stirringthe reaction stirred for another 24 hours
  5. customthe reaction was quenched
  6. additionby adding 1500 mL H2O
  7. customto separate
  8. customThe aqueous layer, pH=13, was separated
  9. additionneutralized by addition of 12N HCl
  10. customto obtain pH=7.0
  11. customat which point a phase separation
  12. concentration2-(2-chlorobenzyl) butanoic acid was concentrated in the organic layer
  13. customSynthesis of 2-ethyl-7-chloroindene

Sources & evidence

ORD record
ord-4e9ce10840114653bf1e5f5d0c9ce540
Source dataset
uspto-grants-2002_10
Patent number
US06465700B1

Reaction notes

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